The authors explored the hypothesis that functional behavior of childhood brain tumors can be estimated by serial analysis of imaging (thallium-201 [201Tl] single-photon emission computed tomography and magnetic resonance imaging [MRI]) examinations. Seventy-five patients diagnosed on clinical or histologic grounds were monitored for a period of 1 day to 3.9 years (mean +/- S.D. = 1.39 +/- 1.10 years). Abnormal 201Tl uptake appeared to denote a subgroup of lesions with distinctly greater mortality and morbidity. Of 201Tl-positive patients, 17% died within the course of this study; no deaths occurred among the 201Tl-negative group. Other parameters of disease outcome also clearly separated the 201Tl-positive and 201Tl-negative groups, with the former demonstrating a 50% shorter period of recurrence-free survival from the time of diagnosis (two-tailed t test, P < 0.01). Significant enhancement with paramagnetic contrast agents paralleled 201Tl positivity in correlating with greater mortality but failed to predict duration of recurrence-free survival. The authors conclude that 201Tl activity provides significant predictive information of the expected biologic behavior of childhood brain tumors, both for duration of recurrence-free survival and for estimated life expectancy. This information complements and extends data provided by MRI enhancement patterns.